Ofatumumab vs Physician's Choice in Subjects With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia
The purpose of this study is to confirm the clinical benefit observed in the pivotal registration study, Hx-CD20-406. The Committee for Medicinal Products for Human Use (CHMP) required that a randomized study be conducted in CLL patients with bulky fludarabine-refractory disease as a specific obligation for grant of conditional approval for ARZERRA™ in the European Union (EU). This study will compare ofatumumab with the physicians' choice of therapy.
Leukaemia, Lymphocytic, Chronic
Drug: Physicians' Choice
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy Versus Physicians' Choice in Patients With Bulky Fludarabine-Refractory Chronic Lymphocytic Leukaemia (CLL)|
- Progression-free survival [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]
- Overall response rate [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]
- The number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Approximately 44 months ] [ Designated as safety issue: Yes ]
- Changes in patient reported outcome measures [ Time Frame: Approximately 44 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Ofatumumab IV, initial dose 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks. After 24 weeks of ofatumumab treatment, patients who have achieved at least stable disease or better, and whom the investigator would deem appropriate for the therapy to continue, would undergo a second randomisation (2:1) to either 1) an additional ofatumumab dose regimen of 2000 mg once every 4 weeks for up to an additional 24 weeks, or 2) no further therapy (i.e. observation only).
Active Comparator: Physicians' Choice
Physicians' choice of treatment
Drug: Physicians' Choice
Non-ofatumumab containing regimen as per physicians' choice for up to 6 months. Permitted therapies include treatments approved for CLL, and well established standards of care for CLL.
Patients with CLL that is refractory to fludarabine have few treatment options and a poor prognosis. There is a continued need for new therapies for these CLL patients, as demonstrated by the limited responses and substantial toxicities with existing therapies. This is supported by the lack of a consensus around standard of care treatment for CLL patients with bulky fludarabine-refractory disease. The objective of this study is to confirm the response rate and disease control in the refractory setting through a controlled trial comparing ofatumumab with the physicians' choice of therapy in fludarabine-refractory, bulky lymphadenopathy patients. After 24 weeks of treatment with ofatumumab, patients will be further randomized to either extended ofatumumab treatment or observation. Patients on the physicians' choice arm will have the option of receiving ofatumumab if they experience progressive disease.